Promoting high-quality pain treatment trials through mentorship of junior investigators: A focus on study conduct and method development

项目总结/摘要 慢性疼痛影响20-30%的美国成年人。不幸的是，现有的疼痛治疗往往只是适度的， 最多有效，许多人不能忍受相关的不良副作用。阿片类药物的使用 用于治疗慢性疼痛的止痛药至少部分地导致了目前的阿片类药物危机， 和他们的家人和朋友，并强调需要发展 新型的非成瘾性疼痛疗法美国国立卫生研究院通过强调高- 高质量的临床试验，包括新的生物标志物和终点，以促进发展， 有效的疼痛治疗。为了推动这一努力，NIH建立了早期疼痛临床研究项目， 网络（EPPIC-网络），提供一个强大的和随时可用的知识社区和基础设施 用于快速设计和执行疼痛治疗的II期临床试验。本申请的PI是 罗切斯特大学EPPIC网络专业临床中心（UR EPPIC网络）的MPI，提供了一个独特的 培训学员进行多中心疼痛临床试验的机会。此外，PI正在进行的项目 的研究解决了对疼痛试验的条件特异性，临床有意义的结局指标的需求， 协同EPPIC网络的努力（1）作出宝贵的贡献，临床疼痛研究领域和（2） 提供一系列临床疼痛研究的培训机会。K24提案的总体目标是提供 为初级研究者提供指导和研究机会，以增加熟练的临床研究人员的数量。 疼痛研究人员谁可以设计，进行，分析和传播高质量的疼痛临床试验的结果， 并反过来加速慢性疼痛的新疗法的发展。Aim 1将利用UR EPPIC- Net培训研究人员进行高质量慢性疼痛治疗临床试验的必要技能。 目标2和3是研究项目，重点是开发工具，以改善2慢性疼痛的临床试验 存在很少有效疗法的病症（即，化疗引起的周围神经病变（CIPN）， 神经源性间歇性跛行（NIC），一种表型独特的神经性慢性腰痛 综合征）。具体而言，目标2调查的信度和效度的措施，平衡，下肢 用于评估功能状态或表征疼痛机制的条件性疼痛调节 在CIPN患者中。目的3调查临床相关的，基于加速度计的结果的有效性， 妮珂这两个目标都利用了PI当前项目的数据， PI的学员有机会获得数据分析，解释和传播的经验， 通过手稿和演讲的临床疼痛研究结果。K24提案概述了PI的计划， 高度协作和支持的研究环境。

PROJECT SUMMARY / ABSTRACT Chronic pain impacts 20-30% of U.S. adults. Unfortunately, available pain treatments tend to be only moderately effective at best and many individuals cannot tolerate the associated adverse side effects. The use of opioid analgesics for treatment of chronic pain contributed, at least in part, to the current opioid crisis, affecting both individuals with pain and their family members and friends, and highlighting the need for the development of novel, non-addictive pain therapies. The NIH responded to this need by emphasizing the importance of high- quality clinical trials that incorporate novel biomarkers and endpoints in order to promote the development of effective pain therapies. To drive this effort, the NIH established the Early Phase Pain Investigation Clinical Network (EPPIC-Net) to provide a robust and readily accessible knowledgeable community and infrastructure for rapid design and performance of phase II clinical trials of pain treatments. The PI of this application is the MPI of the University of Rochester EPPIC-Net Specialized Clinical Center (UR EPPIC-Net), providing a unique opportunity to train mentees in the conduct of multisite pain clinical trials. Furthermore, the PI’s ongoing program of research addresses the need for condition-specific, clinically-meaningful outcome measures for pain trials and synergizes with EPPIC-Net efforts to (1) make valuable contributions to the field of clinical pain research and (2) offer a range of training opportunities in clinical pain research. The overall goal of this K24 proposal is to provide mentoring and research opportunities for junior investigators in order to increase the number of skilled clinical pain researchers who can design, conduct, analyze, and disseminate results of high-quality pain clinical trials, and in turn accelerate the development of novel therapies for chronic pain. Aim 1 will leverage the UR EPPIC- Net to train researchers on the necessary skills to conduct high-quality clinical trials for chronic pain therapies. Aims 2 and 3 are research projects focused on developing tools to improve clinical trials for 2 chronic pain conditions for which few effective therapies exist (i.e., chemotherapy-induced peripheral neuropathy (CIPN) and neurogenic intermittent claudication (NIC), a phenotypically-distinct, neuropathic chronic low back pain syndrome). Specifically, Aim 2 investigates the reliability and validity of measures of balance, lower limb sensation, and conditioned pain modulation for evaluating functional status or characterizing pain mechanisms in patients with CIPN. Aim 3 investigates the validity of clinically-relevant, accelerometry-based outcomes for NIC. Both of these aims leverage data from the PI’s current projects, providing efficient and valuable opportunities for the PI’s mentees to gain experience with data analyses, interpretation, and dissemination of clinical pain research findings via manuscripts and presentations. The K24 proposal outlines the PI’s plan for a highly collaborative and supportive research environment.